The Carcinogenicity of Automotive Gasoline - Evaluation and Rationale

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Mono138-Mono01-Automotive-gasoline.pdf

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6. Eval‎uation and Rationale

6.1 Cancer in humans
There is sufficient evidence in humans for the carcinogenicity of automotive gasoline. Automotive gasoline causes acute myeloid 
leukaemia and cancer of the urinary bladder in adults. Positive associations have been observed for acute lymphoblastic leukaemia in children, and (in adults) non-odgkin lymphoma (including chronic lymphocytic leukaemia), multiple myeloma, myelodysplastic syndrome, and cancers of the stomach and kidney.

6.2 Cancer in experimental animals
There is sufficient evidence in experimental animals for the carcinogenicity of automotive gasoline.

6.3 Mechanistic evidence
There is strong mechanistic evidence for the key characteristics of carcinogens in exposed humans and experimental systems.

6.4 Overall eval‎uation
Automotive gasoline is carcinogenic to humans (Group 1).

6.5 Rationale
The Group 1 eval‎uation for automotive gasoline is based on sufficient evidence for cancer in humans and also on the combination of sufficient evidence for cancer in experimental evidence and strong mechanistic evidence for key characteristics of carcinogens in exposed humans. There was sufficient evidence in humans that gasoline exposure causes acute myeloid leukaemia and bladder cancer in adults. This evidence derived mainly from studies in high-ncome countries on occupational exposure to gasoline and in workers (e.g. service station attendants) who had high gasoline exposure and for whom there was less concern about carcinogenic co-exposures in the workplace. There was also limited evidence in humans for non-Hodgkin lymphoma (including chronic lymphocytic leukaemia), multiple myeloma, myelodysplastic syndrome, and cancers of the stomach  and kidney,  based largely on the same types of study. There was also limited evidence for acute lymphoblastic leukaemia in children, on the basis of studies of parental exposure during pregnancy, exposure during childhood, or close residential proximity to service stations.
The sufficient evidence in experimental animals is based on an increase in the incidence of malignant neoplasms and a combination of benign and malignant neoplasms in both sexes of two species (mouse and rat) in multiple studies, including one GLP study. There is strong mechanistic evidence, on the basis of consistent and coherent evidence for the key characteristics of carcinogens, that automotive gasoline is genotoxic, induces oxidative stress, and induces chronic inflammation provided by studies in exposed humans, mainly service station attendants. Additionally, in experimental systems, automotive gasoline induces oxidative stress; induces chronic inflammation; and alters cell proliferation, cell death, or nutrient supply. There is suggestive evidence that automotive gasolineinduces epigenetic alterations, is immunosuppressive, and modulates receptor-mediated effects.